Corticosterone supplementation reduced selective protein kinase C isoform expression in the epidermis of...

Previous research in this laboratory demonstrated elevated plasma corticosterone and reduced protein kinase C (PKC) activity and selective isoform expression in the epidermis of dietary energy-restricted mice. Because PKC is implicated in skin carcinogenesis and because both energy restriction and glucocorticoid hormone inhibit skin carcinogenesis, the purpose of the present research was to determine whether the elevated glucocorticoid hormone in the energy-restricted mouse contributed to the changes in PKC protein expression. Two strategies were used to control corticosterone in adrenalectomized mice: (a) corticosterone-containing pellets were implanted in mice, and a dose response increase in corticosterone was observed with 5-, 10-, and 35-mg corticosterone implants with average peak values of 68 +/- 22 ng/ml (P < 0.01); and (b) corticosterone was administered in the drinking water, and plasma corticosterone was elevated in a dose-dependent manner in mice killed at 6:00-6:30 p.m. (P < 0.01; peak values of 300-400 ng/ml). The expression of PKCalpha, PKCdelta, and PKCepsilon protein were not consistently altered by corticosterone with the two strategies. PKCeta protein expression was elevated in the adrenalectomized mice administered 3 or 60 microg of corticosterone/ml in drinking water (P < 0.01). PKCzeta protein expression was reduced by all doses of corticosterone in the implant or drinking water (P < 0.05), and a reduction of 41% was achieved with the mice administered 60 microg of corticosterone/ml in drinking water. In mice fed control or energy-restricted diet, with or without adrenalectomy, PKCzeta protein was reduced in sham-operated, energy-restricted mice in comparison with control diet, sham-operated mice (P < 0.02), whereas PKCzeta protein was not significantly different between adrenalectomized control and adrenalectomized, energy-restricted mice. These data indicate that administration of corticosterone in drinking water most closely mimicked the circulating corticosterone and epidermal PKC changes observed in dietary energy restriction. Elevated plasma glucocorticoid levels in the dietary energy-restricted mouse may contribute to the alteration of PKC protein levels in the epidermis.